Background: The enlarged and globular brain is the most distinctive anatomical feature in human evolution that set us apart from our extinct and extant modern human relatives. In a petite evolutionary time the magnitude of human brain is three fold expanded as compared to our closest living kin chimpanzee. Major episodes of human brain size expansion occurred during the upper Pliocene to early Pleistocene era and yet again in middle Pleistocene epochs. The exact genetic basis of these evolutionary changes that bifurcate the highly cognitive human brain from supposedly lesser cognitive nonhuman hominids brain still remain enigmatic. However, it is presumed that complex and larger human brain emerged by essential changes in genes and noncoding regulatory elements. One approach to comprehending the evolution of human brain is to scrutinize the evolution of genes indispensable for normal brain development. Although brain development is genetically complex process, genes associated with early brain development are the best candidate genes in order to understand the mechanism involved in the evolutionary expansion of human brain size. Primary microcephaly genes were selected as their key role in early brain development and mutations in these genes cause severe reduction in cerebral cortex size that is most notably expanded during recent human history. The brain size of microcephalic patients is similar with the size of Pan troglodyte brain and the very early hominid the gracile australopithecine Australopithecus afarensis (average brain size of Australopithecines is 450 cm3), suggesting that primary microcephaly genes likely to have been evolutionary targets in the enlargement of human brain evolution. In this study, the implications of primary microcephaly genes in the evolutionary enlargement of human brain size has been explored by executing a comprehensive evolutionary analysis on ten newly identified microcephaly genes (WDR62, STIL, CEP135, ZNF335, PHC1, CDK6, SASS6, MFSD2A, CIT, and KIF14) across 48 euthrian species. Subsequently also try to explored what are the mechanisms that associate the evolutionary expansion of human brain size with Parkinson‘s disease by studying the molecular evolution of Parkinson‘s disorder linkedalpha synuclein gene. Results: By employing codon substitutions site models based on maximum likelihood method, signatures of pervasive positive selection were identified in five MCPH genes (KIF14, ZNF335, SASS6, CIT and KIF14). For primates, positive selection was found solely in KIF14. Whereas, in nonprimate placental mammals four genes STIL, ZNF335, SASS6, and CIT have exhibit the signature of adaptive evolution. However, pervasive positive selection has acted in STIL, ZNF335 and KIF14 for placental mammals. This study also identified acceleration in the coding sequences of WDR62 and STIL for human terminal branch both by codon substitutions and frequency based methods. However, acceleration in STIL gene is not significant by codon substitutions based method. Furthermore, the signatures of divergent selection constraints between clades are significant for only two genes STIL and SASS6. In the present study, in an endeavor to elucidate whether and why Parkinson‘s disorder affects solely Homo sapiens. Evolutionary study of Parkinson‘s disease associated α synuclein gene revealed that α synuclein gene has been originated specifically at the root of jawed vertebrates and no evolutionary substitutions was accumulated in the α synuclein amino acid sequence during the last 35 million years of evolution. Furthermore, structural dynamics enlighten that during the course of vertebrate evolutionary history, region of amino terminal domain (32 to 58 amino acids) of α synuclein was continuously evolved at structural level, in spite of high sequence conservation at sequence level. Conclusion: This study concluded that evolutionary enlargement of human brain size during Pliocene-Pleistocene period might have not associated to the human MCPH coding sequences exclusively. The joint human specific changes in coding and noncoding regions of human microcephaly loci might have been conducive to the modification in the function of MCPH genes in humans that likely to be responsible for the human brain evolution during the last two million years. Current study on evolution of α synuclein gene provide that region encompassing 3258 amino acid residues of amino terminal domain is critical for normal cellular function and Parkinson‘s disease pathogenesis.
مسز سروجنی نیڈو افسوس ہے کہ ہماری قومی عمارت کا ایک اور ستون گرگیا اور ۲؍ مارچ کو مسز سروجنی نیڈو ہم سے رخصت ہوگئیں وہ عورت تھیں مگر اپنے اوصاف اور خصوصیات میں بہتیرے مردوں سے بڑھ کر تھیں، وہ انگریزی زبان کی نازک خیال شاعرہ، سحرطراز خطیبہ، سیاسیات کی ماہر، جنگ آزادی کی سرفروش سپاہی اور ہندومسلم اتحاد کا عملی نمونہ تھیں، انھوں نے آزادی کی جنگ میں مردوں کے دوش بدوش قیدوبند کی مصیبتیں جھیلیں، وہ فرقہ ورانہ جذبات سے بلند اور صلح کل تھیں، ان کا دل بڑا وسیع تھا، اس میں مسلمانوں کے لئے بھی جگہ تھی، مسلمانوں کے ساتھ ہمیشہ ان کے دوستانہ تعلقات رہے، اور اس فرقہ ورانہ دور میں بھی ان کے خیالات اور طرزعمل میں کوئی تبدیلی نہیں ہوئی تھی، ہندو مسلمانوں کے بعض اختلافی مسائل میں ان کے ذاتی خیالات حکومت کی پالیسی سے مختلف تھے، جن کو وہ صاف طریقہ سے ظاہر نہ کرسکتی تھیں، لیکن ان کی جھلک ان کی تقریروں میں نظر آجاتی تھی، وہ مغربی تعلیم یافتہ تھیں، ان کی ساری زندگی سیاسی میدان میں گزری، اس کے باوجود ان میں نسوانی اور مشرقی خصوصیات موجود تھیں، دل میں نسوانی مہرومحبت، طبیعت میں خلق و مروت، مزاج میں شگفتگی و خوش اخلاقی اور تہذیب و معاشرت میں مغربی آب و رنگ کے ساتھ مشرقی روح جھلکتی تھی، وہ اپنے طرز عمل سے ہندو مسلمان دونوں میں مقبول تھیں اور دونوں کا اعتماد ان کو حاصل تھا، اس لئے ان کی موت دونوں کا قومی حادثہ ہے، ہوا کا رخ دیکھتے ہوئے اب ایسی شخصیتوں کا پیدا ہونا بظاہر مشکل معلوم ہوتا ہے۔ (شاہ معین الدین ندوی، مارچ ۱۹۴۹ء)
Virus COvid-19 sedang menjadi perhatian dunia termasuk di Indonesia sehingga pemerintah mengeluarkan berbagai kebijakan untuk mencegah penyebaran virus Covid-19. Kebijakan tersebut diantaranya penetapan PSBB (pembatasan sosial skala besar) sehingga semua kegiatan dialihkan ke rumah atau Work From Home (WFH) termasuk kegiatan perkulihan, dialihkan menjadi pembelajan via online. Karena dipindahkannya proses perkuliahan ke rumah menjadikan mahasiswa dituntut untuk mengelola serta mengatur belajarnya sendiri (Self Regulated Learning) selama masa Covid-19. Pengumpulan data pada penelitian ini menggunkan angket dan disebarkan secara onlien melalui google form. Penelitian ini menggunkan metode kuantitatif deskriptif dengan subjek penelitian mahasiswa angkatan 2017, 2019, dan 2018, jurusan psikologi Universitas Negeri Padang. Hasil pada penelitian ini menunjukan bahwa self regulated learning pada mahasiswa berada pada kategori sedang dengan persentase sebesar 61, 4%, kategori tinggi dengan persentase 38, 6%. Hel ini menunjukkan bahwa pada umunya mahasiswa sudah memahami dan melaksanakan self regulated learning pada kegiatan perkulihaan selama masa pandemi.
New drug entities with poor aqueous solubility are becoming more prevalent as result of high-throughput screening in drug discovery. Poor aqueous solubility presents significant challenges, as it reduces the absorption and oral bioavailability. Several formulation approaches have been employed to overcome the limitations of low dissolution rate and/or solubility including; pH-adjustment, co-solvents, surfactants, inclusion complexes, lipid-based formulations i.e. Solid lipid nanoparticles (SLNs) and Nanostructured lipid carriers (NLCs), and nano-suspensions. In this study efforts are made for the selection of formulation approach based on the drug properties and the required specifications of the final dosage form. Among these formulation approaches solid lipid nanoparticles were selected with the aim of improving solubility/bioavailability of the poorly water-soluble drugs; BCS-II (Niclosamide) and BCS-IV (Sulfasalazine). Two different techniques i.e. Micro-emulsion Technique and Solvent Emulsification Diffusion Technique were used to fabricate SLNs. The SLNs formulations were characterized by Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (P-XRD) and Fourier Transform Infrared (FT-IR). The SLNs formulations loaded with Niclosamide and Sulfasalazine were successfully converted to solid dosage form followed by similarity study. In-vitro studies of SLNs formulations in comparison with marketed dosage form showed improvement in solubility and dissolution while the in-vivo studies confirmed improved oral bioavailability. Niclosamide loaded SLNs fabricated by Micro Emulsion Technique having particle size 204.2 ± 2.2 nm, polydispersity index 0.328 ± 0.02, zeta potential -33.16 ± 2mv, entrapment efficiency 84.4 ± 0.02%, and drug loading capacity 5.27 ± 0.03% were obtained. Different kinetic models showed zero order kinetics and Case-II transport mechanism. In-vivo pharmacokinetic study showed 2.15-fold increase in peak plasma concentration for Niclosamide loaded SLNs while relative bioavailability (Fr) of 11.08. Fabrication of Niclosamide loaded SLNs using Solvent Emulsification Diffusion Technique showed particle size 208.6 ± 2.2 nm, polydispersity index 0.376 ± 0.04, zeta potential -34.11 ± 1.2 mv, entrapment efficiency 85.4 ± 0.04% and drug loading capacity 3.18 ± 0.04 %. Observed zero order kinetics with case-II transport, the range in the parenthesis might be helpful for the drug release mechanism. 2.04-fold increase in peak plasma concentration was observed in pharmacokinetic study with relative bioavailability (Fr) of 10.59. In case of Sulfasalazine-SLNs prepared by Micro Emulsion Technique having particle size 217.2 ± 3.2nm, PDI 0.373 ± 0.02, zeta potential -35.26 ± 2mV, entrapment efficiency 89.1 ± 0.03% and drug loading capacity 2.87 ± 0.05% were obtained. Kinetic modelling studies showed mixed order kinetics for drug release. Release exponent was more than 0.89, regarded as Super Case-II diffusion mechanism. In-vivo pharmacokinetic study showed 2.43-fold increase in oral bioavailability of sulfasalazine as SLN formulation compared to commercial product. Solvent Emulsification Diffusion Technique was used to fabricate Sulfasalazine loaded SLNs, showed particle size 202.3 ± 2.2 nm, PDI 0.376 ± 0.02, zeta potential -35.82 ± 2 mV, entrapment efficiency 86.3 ± 0.02% and drug loading capacity 3.03 ± 0.04%. Zero order kinetics and Case-II transport mechanism for drug release was observed with 1.86-fold increase in peak plasma concentration during pharmacokinetic study. These studies validated that, SLNs as nanoparticulate drug delivery system enhanced oral bioavailability of Niclosamide and Sulphasalazine. Hence, these studies provide new strategies for the oral bioavailability of hydrophobic drugs.