The role of perlecan and endorepellin in the control of tumor angiogenesis and endothelial cell autophagy.

During tumor growth and angiogenesis there is a dynamic remodeling of tissue architecture often accompanied by the release of extracellular matrix constituents full of biological activity. One of the key constituents of the tumor microenvironment is the large heparan sulfate proteoglycan perlecan. This proteoglycan, strategically located at cell surfaces and within basement membranes, is a well-defined pro-angiogenic molecule when intact. However, when partially processed by proteases released during cancer remodeling and invasion, the C-terminal fragment of perlecan, known as endorepellin, has opposite effects than its parent molecule. Endorepellin is a potent inhibitor of angiogenesis by exerting a dual receptor antagonism by simultaneously engaging VEGFR2 and α2β1 integrin. Signaling through the α2β1 integrin leads to actin disassembly and block of endothelial cell migration, necessary for capillary morphogenesis. Signaling through the VEGFR2 induces dephosphorylation of the receptor via activation of SHP-1 and suppression of downstream proangiogenic effectors, especially attenuating VEGFA expression. A novel and emerging role of endorepellin is its ability to evoke autophagy by activating Peg3 and various canonical autophagic markers. This effect is specific for endothelial cells as these are the primary cells expressing both VEGFR2 and α2β1 integrin. Thus, an endogenous fragment of a ubiquitous proteoglycan can regulate both angiogenesis and autophagy through a dual receptor antagonism. The biological properties of this natural endogenous protein place endorepellin as a potential therapeutic agent against cancer or diseases where angiogenesis is prominent

Linear cyclodextrin polymer prodrugs as novel yherapeutics for Niemann-Pick type C1 disorder

Niemann-Pick Type C1 disorder (NPC) is a rare lysosomal storage disease characterized by the accumulation of cholesterol in lysosomes. NPC has no FDA approved treatments yet, however 2-hydroxypropyl-β-cyclodextrin (HPβCD) has shown efficacy for treating the disease in both mouse and feline NPC models and is currently being investigated in late stage clinical trials. Despite promising results, therapeutic use of HPβCD is limited by the need for high doses, ototoxicity and intrathecal administration. These limitations can be attributed to its poor pharmacokinetic profile. In the attempt to overcome these limitations, we have designed a β-cyclodextrin (βCD) based polymer prodrugs (ORX-301) for an enhanced pharmacokinetic and biodistribution profile, which in turn can potentially provide an improved efficacy at lower doses. We demonstrated that subcutaneously injected ORX-301 extended the mean lifespan of NPC mice at a dosage 5-fold lower (800 mg/kg, body weight) the HPβCD dose proven efficacious (4000 mg/kg). We also show that ORX-301 penetrates the blood brain barrier and counteracts neurological impairment. These properties represent a substantial improvement and appear to overcome major limitations of presently available βCD-based therapy, demonstrating that this novel prodrug is a valuable alternative/complement for existing therapies

WTASR: Wavelet Transformer for Automatic Speech Recognition of Indian Languages

Automatic speech recognition systems are developed for translating the speech signals into the corresponding text representation. This translation is used in a variety of applications like voice enabled commands, assistive devices and bots, etc. There is a significant lack of efficient technology for Indian languages. In this paper, an wavelet transformer for automatic speech recognition (WTASR) of Indian language is proposed. The speech signals suffer from the problem of high and low frequency over different times due to variation in speech of the speaker. Thus, wavelets enable the network to analyze the signal in multiscale. The wavelet decomposition of the signal is fed in the network for generating the text. The transformer network comprises an encoder decoder system for speech translation. The model is trained on Indian language dataset for translation of speech into corresponding text. The proposed method is compared with other state of the art methods. The results show that the proposed WTASR has a low word error rate and can be used for effective speech recognition for Indian language

Gas Under Right Hemidiaphragm: A Rare Presentation of Unruptured Liver Abscess

A perforated liver abscess mimics hollow viscus perforations. It may be accompanied by pneumoperitoneum and peritonitis. A hollow viscus perforation appears to be the most common cause of gas under diaphragm. In about 10% of the cases, it can be due to rare abdominal and extra-abdominal causes. One of the causes could be intra-abdominal infection caused by gas-forming organisms. We are reporting a rare case of pneumoperitoneum resulting from an unruptured liver abscess in an old male with no comorbidity. An unruptured pyogenic right lobe liver abscess in a 70-year-old male was accompanied by X-ray flat plate abdomen features suggestive of free gas under the right hemidiaphragm. Culture of the pus drained from liver abscess grew Klebsiella sensitive to piperacillin and tazobactam, and antibiotic treatment was administered

Performance Evaluation of Chaos Based IDMA Scheme Using Joint Turbo Equalization Over Frequency Selective Fading Channel

This paper proposed the analysis of a new chaos based interleave division multiple access (CB-IDMA) wireless communication system. It also proposed the use of joint turbo equalization to mitigate the effect of intersymbol interference (ISI) in deep faded frequency selective channel. In this study, the proposed CB-IDMA system used the chaotic Tent map for the design of a robust interleaver, which produces low correlation among the users and yields better bit error rate performance. The proposed structure combined the joint turbo equalization for the cancellation of ISI and multiple access interference (MAI), which was observed as the main impediment to successful IDMA communication over frequency selective multipath fading channel. Two types of frequency domain equalizers were considered for performance evaluation; zero forcing (ZF) and minimum mean square error (MMSE) equalizer. Simulation experiments were performed in MATLAB and the results demonstrated that the proposed CB-IDMA system with joint turbo equalization may be preferred in deep fading environment

Graham’s patch omentopexy versus modified Graham’s patch omentopexy in duodenal perforation – A comparative study

Background: Peptic ulcer perforation is a serious complication which affects 2–10% of peptic ulcer patients. Peptic ulcer perforation presents with an overall mortality of 10% although various authors had reported incidence between 1.3% and 20%. Being a life-threatening complication of peptic ulcer disease, it needs special attention with prompt resuscitation and appropriate surgical management if morbidity and mortality are to be contained. Aims and Objectives: The aim of the study was to the comparative study of Graham’s omentopexy versus modified Graham’s omentopexy in duodenal perforation. Materials and Methods: This prospective and single-center study was done in Birsa Munda, GMC Shahdol Madhya Pradesh from 2021 to 2023 for 2 years of periods. A total of 160 patients divided into two groups-Graham’s omentopexy 80 cases group “A” and modified Graham’s omentopexy 80 cases group “B.” Results: One hundred and forty-six (91%) were male and 14 (9%) were female with M:F Ratio 10:1. Most of the patients were 20–78 years of age in both groups. Post-operative leakage was 7.5% and 1.25%, respectively. Mortality rate in Group A (3.75%) and in Group B (1.25%). The overall mortality rate was 7.14%. In this study, average hospital stay was 12.4 days in Group A and 9.0 days in Group B. Conclusion: This study showed that modified Graham’s patch repair is as effective as Graham’s patch repair in terms of the mean operative time period, the timing of oral feed allow, and mean hospital stay timing

EphA2 is a functional receptor for the growth factor progranulin.

Although the growth factor progranulin was discovered more than two decades ago, the functional receptor remains elusive. Here, we discovered that EphA2, a member of the large family of Ephrin receptor tyrosine kinases, is a functional signaling receptor for progranulin. Recombinant progranulin bound with high affinity to EphA2 in both solid phase and solution. Interaction of progranulin with EphA2 caused prolonged activation of the receptor, downstream stimulation of mitogen-activated protein kinase and Akt, and promotion of capillary morphogenesis. Furthermore, we found an autoregulatory mechanism of progranulin whereby a feed-forward loop occurred in an EphA2-dependent manner that was independent of the endocytic receptor sortilin. The discovery of a functional signaling receptor for progranulin offers a new avenue for understanding the underlying mode of action of progranulin in cancer progression, tumor angiogenesis, and perhaps neurodegenerative diseases

Breeding for increased nitrogen-use efficiency: a review for wheat (T. aestivum L.)

Nitrogen fertilizer is the most used nutrient source in modern agriculture and represents significant environmental and production costs. In the meantime, the demand for grain increases and production per area has to increase as new cultivated areas are scarce. In this context, breeding for an efficient use of nitrogen became a major objective. In wheat, nitrogen is required to maintain a photosynthetically active canopy ensuring grain yield and to produce grain storage proteins that are generally needed to maintain a high end-use quality. This review presents current knowledge of physiological, metabolic and genetic factors influencing nitrogen uptake and utilization in the context of different nitrogen management systems. This includes the role of root system and its interactions with microorganisms, nitrate assimilation and its relationship with photosynthesis as postanthesis remobilization and nitrogen partitioning. Regarding nitrogen-use efficiency complexity, several physiological avenues for increasing it were discussed and their phenotyping methods were reviewed. Phenotypic and molecular breeding strategies were also reviewed and discussed regarding nitrogen regimes and genetic diversity

Studies on Phantom Vibration and Ringing Syndrome among Postgraduate Students

Phantom vibrations and ringing of mobile phones are prevalent hallucinations in the general population. They might be considered as a normal brain mechanism. The aim of this study was to establish the prevalence of Phantom vibrations and ringing syndrome among students and to assess factors associated it. The survey of 300 postgraduate students belonging to different field of specialization was conducted at Kurukshetra University. 74% of students were found to have both Phantom vibrations and ringing syndrome. Whereas 17% of students felt Phantom vibration exclusively and 4% students face only Phantom ringing syndrome. Both the syndrome occurs more fervent in students who kept their mobile phone in shirt or jean pocket than to who kept mobile in handbag. 75% of students felt vibration or ringing even when the phone is switched off or phone was not in their pocket. Also the frequency of both the syndrome is directly proportional to the duration of mobile phone use and person emotional behavior. Although most of students agree that the Phantom syndrome did not bother them but some students deals with anxiety when they feel symptoms associated with Phantom syndrome. By using mobile phones in proper way, one can avoid these syndromes, or at least can ameliorate the symptoms