Feng Zhang

Bio: Feng Zhang is an academic researcher from Fudan University. The author has contributed to research in topics: Medicine & Materials science. The author has an hindex of 172, co-authored 1278 publications receiving 181865 citations. Previous affiliations of Feng Zhang include Cincinnati Children's Hospital Medical Center & Nanjing Medical University.

Systems, methods and compositions for optical stimulation of target cells

Abstract: Methods, systems and devices are implemented in connection with light-responsive ion channel molecules. One such method is implemented using a light-activated ion channel molecule that responds to a light stimulus. The method includes engineering the light-activated ion channel molecule in a cell; and activating the ion channel molecule, in response to light stimulus that is provided to the ion channel molecule and that has properties that do not activate a ChR2 ion channel, to allow ions to pass through the light-activated ion channel molecule.

Partial deletions are associated with an increased risk of complete deletion in AZFc: a new insight into the role of partial AZFc deletions in male infertility

Abstract: Background: The AZFc region on the human Y chromosome has been found to be functionally important in spermatogenesis. Complete AZFc deletion is one of the most frequent causes of male infertility and the roles of partial AZFc deletions (gr/gr and b2/b3 deletions) in spermatogenesis are controversial. Methods: To further study the roles of partial AZFc deletions in spermatogenic impairment and the relationship between complete and partial AZFc deletions, these deletions were typed and quantitative analysis of DAZ gene copies and Y chromosome haplogrouping were performed for seven pedigrees of complete AZFc deletion carriers, comprising 296 infertile and 280 healthy Chinese men. Results: Neither the gr/gr nor the b2/b3 deletion was found to be associated with spermatogenic failure. In one pedigree, a complete AZFc deletion was observed to result from the gr/gr deletion, suggesting that complete deletions of AZFc can be preceded by partial deletions. In addition, a new gr/gr-deleted Y haplogroup Q1 was identified and the reported fixation of the b2/b3 deletion in haplogroup N confirmed. The frequency of complete AZFc deletion in haplogroups Q1 and N was significantly higher than that in the other haplogroupsm with fewer partial deletions. Duplications of DAZ gene copies were also observed in this study. Conclusions: To date, these observations comprise the first evidence showing that partial AZFc deletions can increase the risk of complete AZFc deletion. The susceptibility of partial AZFc deletions to complete AZFc deletion deserves further examination, especially in the populations or Y haplogroups abundant in partial AZFc deletions.

Bi-allelic Mutations in TTC21A Induce Asthenoteratospermia in Humans and Mice.

Abstract: Male infertility is a major concern affecting human reproductive health. Asthenoteratospermia can cause male infertility through reduced motility and abnormal morphology of spermatozoa. Several genes, including DNAH1 and some CFAP family members, are involved in multiple morphological abnormalities of the sperm flagella (MMAF). However, these known genes only account for approximately 60% of human MMAF cases. Here, we conducted further genetic analyses by using whole-exome sequencing in a cohort of 65 Han Chinese men with MMAF. Intriguingly, bi-allelic mutations of TTC21A (tetratricopeptide repeat domain 21A) were identified in three (5%) unrelated, MMAF-affected men, including two with homozygous stop-gain mutations and one with compound heterozygous mutations of TTC21A. Notably, these men consistently presented with MMAF and additional abnormalities of sperm head-tail conjunction. Furthermore, a homozygous TTC21A splicing mutation was identified in two Tunisian cases from an independent MMAF cohort. TTC21A is preferentially expressed in the testis and encodes an intraflagellar transport (IFT)-associated protein that possesses several tetratricopeptide repeat domains that perform functions crucial for ciliary function. To further investigate the potential roles of TTC21A in spermatogenesis, we generated Ttc21a mutant mice by using CRISPR-Cas9 technology and revealed sperm structural defects of the flagella and the connecting piece. Our consistent observations across human populations and in the mouse model strongly support the notion that bi-allelic mutations in TTC21A can induce asthenoteratospermia with defects of the sperm flagella and head-tail conjunction.

Identification of uncommon recurrent Potocki-Lupski syndrome-associated duplications and the distribution of rearrangement types and mechanisms in PTLS.

Abstract: Nonallelic homologous recombination (NAHR) can mediate recurrent rearrangements in the human genome and cause genomic disorders. Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) are genomic disorders associated with a 3.7 Mb deletion and its reciprocal duplication in 17p11.2, respectively. In addition to these common recurrent rearrangements, an uncommon recurrent 5 Mb SMS-associated deletion has been identified. However, its reciprocal duplication predicted by the NAHR mechanism had not been identified. Here we report the molecular assays on 74 subjects with PTLS-associated duplications, 35 of whom are newly investigated. By both oligonucleotide-based comparative genomic hybridization and recombination hot spot analyses, we identified two cases of the predicted 5 Mb uncommon recurrent PTLS-associated duplication. Interestingly, the crossovers occur in proximity to a recently delineated allelic homologous recombination (AHR) hot spot-associated sequence motif, further documenting the common hot spot features shared between NAHR and AHR. An additional eight subjects with nonrecurrent PTLS duplications were identified. The smallest region of overlap (SRO) for all of the 74 PTLS duplications examined is narrowed to a 125 kb interval containing only RAI1, a gene recently further implicated in autism. Sequence complexities consistent with DNA replication-based mechanisms were identified in four of eight (50%) newly identified nonrecurrent PTLS duplications. Our findings of the uncommon recurrent PTLS-associated duplication at a relative prevalence reflecting the de novo mutation rate and the distribution of 17p11.2 duplication types in PTLS reveal insights into both the contributions of new mutations and the different underlying mechanisms that generate genomic rearrangements causing genomic disorders.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …

A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.

Abstract: Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature crRNA that is base-paired to trans-activating crRNA (tracrRNA) forms a two-RNA structure that directs the CRISPR-associated protein Cas9 to introduce double-stranded (ds) breaks in target DNA. At sites complementary to the crRNA-guide sequence, the Cas9 HNH nuclease domain cleaves the complementary strand, whereas the Cas9 RuvC-like domain cleaves the noncomplementary strand. The dual-tracrRNA:crRNA, when engineered as a single RNA chimera, also directs sequence-specific Cas9 dsDNA cleavage. Our study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.